Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study

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• 作者：Vladimir V. Zarubaev^a ; ^{zarubaev@influenza.spb.ru" class="auth_mail" title="E-mail the corresponding author} ; Anatolii S. Morkovnik^b ; Liudmila N. Divaeva^b ; Liubov&rsquo ; A. Karpinskaya^a ; Gennadii S. Borodkin^b
• 关键词：2-Iminobenzimidazolines ; 2-Acylaminobenzimidazoles ; 2-Thioureidobenzimidazoles ; Influenza virus ; Antiviral activity ; Cytotoxicity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：24
• 期：22
• 页码：5796-5803
• 全文大小：479 K

文摘

A series of 1,3-disubstituted 2-iminobenzimidazolines as well as a number of their tautomeric analogs were synthesized. The synthesized compounds were tested for their cytotoxicity against MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09. Based on the results obtained, 50% cytotoxic concentration (CC₅₀), 50% inhibiting concentration (IC₅₀) and selectivity index (SI) were calculated for each compound. It was found that some of synthesized benzimidazole derivatives (7 of 22, 32%) possess strong virus-inhibiting activity against pandemic influenza virus (IC₅₀’s in low micromolar range) with quite moderate cytotoxicity (CC₅₀ in the range of thousands micromoles). Due to their high selectivity (highest SI’s = 50–83) these compounds are of significant interest for further in vivo experiments as well as for further structural optimization and drug development.